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Molecular Dynamics Simulations (molecular + dynamics_simulation)
Kinds of Molecular Dynamics Simulations Terms modified by Molecular Dynamics Simulations Selected AbstractsCoarse Grained Molecular Dynamics Simulation of Electromechanically-Gated DNA Modified Conical NanoporesELECTROANALYSIS, Issue 3 2008Lajos Höfler Abstract Nanopore-based devices are emerging as tools for single molecule manipulation, characterization and chemical analysis. Single or random arrays of chemically modified nanopores have been established as platforms for selective chemical and biosensing. However, it is little known about the orientation and behavior of surface tethered species in the nanopore environment as function of applied transpore voltages. In this study we report on coarse grained modeling of short (5-, 15-mer) DNA modified conical gold nanopores subjected to electrical field gradients of 5 and 50,mV/nm. An electromechanical gating effect in the single stranded DNA modified conical nanopores is predicted, which is due to the obstruction of the tip entrance by DNA strands oriented by the external electrical field. The magnitude of the rectification effect increases with increasing DNA length and decreasing tip diameter of the conical nanopore. The direction of on/off switching was found to be dependent on the location of the immobilized DNAs on the membrane supporting the nanopore. [source] Structure of Polymer Brushes in Cylindrical Tubes: A Molecular Dynamics SimulationMACROMOLECULAR THEORY AND SIMULATIONS, Issue 7 2006Dimitar I. Dimitrov Abstract Summary: Molecular dynamics simulations of a coarse-grained bead-spring model of flexible macromolecules tethered with one end to the surface of a cylindrical pore are presented. Chain length N and grafting density , are varied over a wide range and the crossover from "mushroom" to "brush" behavior is studied for three pore diameters. The monomer density profile and the distribution of the free chain ends are computed and compared to the corresponding model of polymer brushes at flat substrates. It is found that there exists a regime of N and , for large enough pore diameter where the brush height in the pore exceeds the brush height on the flat substrate, while for large enough N and , (and small enough pore diameters) the opposite behavior occurs, i.e. the brush is compressed by confinement. These findings are used to discuss the corresponding theories on polymer brushes at concave substrates. Snapshot picture of a brush grafted inside of a cylinder, for , , displaying different chains in distinct colors in order to be able to distinguish them. Top shows a side view of the cylinder, and the lower part a view of the cross-section. Note that the particles forming the cylindrical wall are not displayed. [source] Molecular Dynamics Simulation of the Fracture in Polymer-Exfoliated Layered Silicate NanocompositesMACROMOLECULAR THEORY AND SIMULATIONS, Issue 3 2006Mo Song Abstract Summary: The MD technique was used to investigate the fracture behavior in fully exfoliated layered silicate (nanoplatelet)-polymer nanocomposites. MD results reveal that the addition of the nanoplatelets can improve the fracture strength of polymers. The interactions between the surface of the nanoplatelets and the segments of the polymer, and the relaxation time of polymer chains have significant influences on the fracture strength of the polymer. For polymers with Tg below room temperature, such as polyurethane, or close to room temperature, such as nylon, the nanoplatelets are always working for the enhancement of the mechanical properties. However, for polymers with Tg above room temperature, such as epoxy and polystyrene, the addition of the nanoplatelets is not working well for toughening these polymers. If the nanoplatelets are to enhance the mechanical properties of these polymers, it is necessary to build up a stress relaxation interface between the polymer and the nanoplatelet in order to reduce the effect of the difference between the relaxation time of nanofillers and that of polymers. Force per area versus distance curves as a function of the difference of the relaxation times of the nanoplatelets and polymer chains. [source] Insight into the Metabolism Rate of Quinone Analogues from Molecular Dynamics Simulation and 3D-QSMR MethodsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2007Hai-Feng Chen Molecular dynamics simulation was applied to investigate the metabolism mechanism for quinone analogues. Favourable hydrogen bonds between ligand and NQO1, and parallel orientation between ligand and flavin adenine dinucleotide could explain the difference of metabolism rate (in ,mol/min/mg) for quinone analogues. This is consistent with the experimental observation (Structure 2001;9:659,667). Then Support Vector Machines was used to construct quantitative structure,metabolism rate model. The model was evaluated by 14 test set compounds. Some descriptors selected by Support Vector Machine, were introduced into standard fields of three-dimensional quantitative structure,metabolism relationship to improve the statistical parameters of three-dimensional quantitative structure,metabolism relationship models. The results show that the inclusion of highest occupied molecular orbital and lowest unoccupied molecular orbital is meaningful for three-dimensional quantitative structure,metabolism relationship models. These in silico absorption, distribution, metabolism and excretion models are helpful in making quantitative prediction of their metabolic rates for new lead compounds before resorting in vitro and in vivo experimentation. [source] Structure and Dynamics of the Cd2+ Ion in Aqueous Solution: Ab Initio QM/MM Molecular Dynamics Simulation.CHEMINFORM, Issue 5 2004Chinapong Kritayakornupong No abstract is available for this article. [source] Contraction Process of an Electroactive Actuator Based on a One Microsecond Atomistic Molecular Dynamics SimulationCHEMISTRY - A EUROPEAN JOURNAL, Issue 9 2007David Zanuy Dr. Abstract The contraction process of an electroactive actuator constituted by calix[4]arene units and quaterthiophene segments has been investigated at the microscopic level by using atomistic molecular dynamics simulations in dichloromethane solution using explicit solvent molecules. Results derived from a 1,,s trajectory of the oxidized and deprotonated actuator indicate that the contraction occurs through a non-concerted mechanism in which each actuating units present in the system behave independently. The efficiency of the contraction process can be reduced by the presence of secondary conformational transitions in the calix[4]arene scaffolds. Accordingly, the drastic reduction of the molecular length expected during the contraction process can be limited by such transitions, which involve the rotational isomerism of a phenolate ring. However, such type of conformational transitions does not compromise the actuator power due to its intrinsic capacity to adopt compact molecular arrangements. On the other hand, the rate of the contraction process is influenced by the presence of solvent molecules, which have been found to reduce it by a factor of about 1000. [source] Ab Initio Molecular Dynamics Simulation of a Water,Hydrogen Fluoride Equimolar MixtureCHEMPHYSCHEM, Issue 1 2005Christian Simon Abstract Hydrogen fluoride and water can be mixed in any proportion. The resulting solutions have unique acidic properties. In particular, hydrogen fluoride undergoes a weak-to-strong acidity transition with increasing concentration of HF. To supplement the knowledge already obtained on dilute or moderately concentrated solutions and gas-phase aggregates, an equimolar mixture is studied here by Car,Parrinello molecular dynamics. The natures of the ions and of the complexes formed in the equimolar liquid were determined. Specifically, H3O+, H5O2+, FHOH2, and HF2,were spontaneously obtained while only hydronium and fluoride ions pre-exist in the equimolar crystal. The behaviour of the proton in the equimolar liquid was compared with mixtures of other proportions simulated previously in an attempt to relate proton dynamics to acidity. In the same way, the behaviour of HF2,was also examined. In this case, proton localization and transfer appeared to be driven by the fluctuating environment of the solvated ion. [source] Molecular Dynamics Simulation of Interaction between Calcite Crystal and Phosphonic Acid MoleculesCHINESE JOURNAL OF CHEMISTRY, Issue 3 2010Jianping Zeng Abstract The interactions between calcite crystal and seven kinds of phosphonic acids, nitrilotris(methylphosphonic acid) (NTMP), nitrilo-methyl-bis(methylphosphonic acid) (NMBMP), N,N -glycine-bis(methylphosphonic acid) (GBMP), 1- hydroxy-1,1-ethylenebis(phosphonic acid) (HEBP), 1-amino-1,1-ethylenebis(phosphonic acid) (AEBP), 1,2-ethylenediamine- N,N,N,,N, -tetrakis(methylphosphonic acid) (EDATMP), and 1,6-hexylenediamine- N,N,N,,N, -tetrakis- (methylphosphonic acid) (HDATMP) have been simulated by a molecular dynamics method. The results showed that the binding energy of each scale inhibitor with the (1l,0) (1l,0) face of calcite crystal was higher than that with (104) face, which has been approved by the analysis of pair correlation functions. The sequence of scale inhibition efficiencies for phosphonic acids against calcite scale is as follows: EDATMP>HDATMP>HEBP>NTMP>GBMP>HEBP>NMBMP, and the growth inhibition on the (1l,0) face of calcite was at the leading status. Phosphonic acids deformed during the binding process, and electrovalent bonds formed between the phosphoryl oxygen atoms in phosphonic acids and the calcium ions on calcite crystal. [source] Short-Range Structure of Yttrium Alumino-Silicate Glass for Cancer Radiotherapy: Car,Parrinello Molecular Dynamics Simulations,ADVANCED ENGINEERING MATERIALS, Issue 7 2010Jamieson K. Christie We present Car,Parrinello molecular dynamics (CPMD) simulations of yttrium alumino-silicate (YAS) glass. Alumino-silicate glass microspheres are used as vectors of yttrium radioisotopes in cancer radiotherapy; understanding in detail how yttrium is bound within the glass network is important to control the unwanted release of radioactive yttrium in the bloodstream. Our simulations, focused on a specific composition relevant to practical applications, show that silicon and aluminum form a disordered glass network, where Si is mainly four-coordinated, whereas, Al is mainly four- and five-coordinated. Yttrium cations have a network-modifying role, disrupting the alumino-silicate network by breaking Si(Al)O bonds and coordinating the resulting non-bridging oxygens (NBO). The local environment of yttrium in the glass turns out to be rather flexible: between five and eight oxygen atoms, with a marked predominance of NBO, are found coordinated to a central Y cation, leading to a corresponding broad and multimodal distribution of OYO angles. [source] Molecular Dynamics Simulations of Amorphous Si,C,N Ceramics: Composition Dependence of the Atomic StructureJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 8 2003Nicoletta Resta We have performed classical molecular dynamics simulations of amorphous Si,C,N materials. The dependence of the local order and of the microstructure on the chemical composition was investigated. Our simulations show that for a stoichiometric nitrogen/silicon ratio equal to or higher than 4/3, the amorphous ceramic separates into different amorphous domains, namely C-rich, SiN-rich, and SiC-rich phases. Below this ratio, the material is composed of mixed structures, homogeneously spread within the material. For a very particular composition range, we found that carbon atoms crystallize into monoatomic graphitic layers surrounding the SiN-rich domains. [source] Dissipative Particle Dynamics Simulations of Polymer Brushes: Comparison with Molecular Dynamics SimulationsMACROMOLECULAR THEORY AND SIMULATIONS, Issue 9 2006Sandeep Pal Abstract Summary: The structure of polymer brushes is investigated by dissipative particle dynamics (DPD) simulations that include explicit solvent particles. With an appropriate choice of the DPD interaction parameters , we obtain good agreement with previous molecular dynamics (MD) results where the good solvent behavior has been modeled by an effective Lennard,Jones potential. The present results confirm that DPD simulation techniques can be applied for large length scale simulations of polymer brushes. A relation between the different length scales and is established. Polymer brush at a solid,liquid interface. [source] Temperature and Pressure Effects on Local Structure and Chain Packing in cis -1,4-Polybutadiene from Detailed Molecular Dynamics SimulationsMACROMOLECULAR THEORY AND SIMULATIONS, Issue 5 2006Georgia Tsolou Abstract Summary: We present results for the temperature and pressure dependence of local structure and chain packing in cis -1,4-polybutadiene (cis -1,4-PB) from detailed molecular dynamics (MD) simulations with a united-atom model. The simulations have been executed in the NPT statistical ensemble with a parallel, multiple time step MD algorithm, which allowed us to access simulation times up to 1 µs. Because of this, a 32 chain C128cis -1,4-PB system was successfully simulated over a wide range of temperature (from 430 to 195 K) and pressure (from 1 atm to 3 kbar) conditions. Simulation predictions are reported for the temperature and pressure dependence of the: (a) density; (b) chain characteristic ratio, Cn; (c) intermolecular pair distribution function, g(r), static structure factor, S(q), and first peak position, Qmax, in the S(q) pattern; (d) free volume around each monomer unit along a chain for the simulated polymer system. These were thoroughly compared against available experimental data. One of the most important findings of this work is that the component of the S(q) vs. q plot representing intramolecular contributions in a fully deuterated cis -1,4-PB sample exhibits a monotonic decrease with q which remains completely unaffected by the pressure. In contrast, the intermolecular contribution exhibits a distinct peak (at around 1.4 Å,1) whose position shifts towards higher q values as the pressure is raised, accompanied by a decrease in its intensity. 3D view of the simulation box containing 32 chains of C128cis -1,4-polybutadiene at density ,,=,0.849 g,·,cm,3 and the conformation of a single C128cis -1,4-PB chain fully unwrapped in space. [source] Molecular Dynamics Simulations of the Orientation and Reorientational Dynamics of Water and Polypyrrole Rings as a Function of the Oxidation State of the PolymerMACROMOLECULAR THEORY AND SIMULATIONS, Issue 1 2005Jose J. López Cascales Abstract Summary: Polypyrrole is one of the most widely-studied conducting polymers due to its steady electrochemical response and good chemical stability in different solvents, including organic and inorganic ones. In this work, we provide for the first time valuable information in atomic detail concerning the steady and dynamic properties of pyrrole rings as a function of the oxidation state of the polymer. The study was carried out by Classical molecular dynamics simulation, where the system was modelled by 256 polypyrrole chains of 10 pyrrole rings each. Water was explicitly introduced in our simulations. Besides the uncharged or reduced state, two steady oxidation states of the polymer have been simulated by introducing a net charge (+1) on 85 and 256 of the polypyrrole chains. To balance the charges emerging in these oxidised states, 85 and 256 chloride ions (Cl,1) respectively, were introduced into the system. From an analysis of the simulated trajectories, the orientation and relaxation times of water and pyrrole rings were evaluated for the different oxidation states of the polymer across the polypyrrole/water interface. The calculated densities for different oxidation states describe the swelling or shrinking process during electrochemical oxidation or reduction respectively. The rotational relaxation times calculated for the polypyrrole rings decrease with increasing oxidation of the polymer, which is in a good agreement with experimental electrochemical data. Almost no variation in pyrrole ring orientation was measured for the different oxidation states of the polymer, even compared with polypyrrole bulk. As regards the water structure in the vicinity of the polypyrrole/water interface, both the orientation and orientation relaxation time were strongly affected by the presence of charges in the polymer. Thus, the water dipole was strongly orientated in the vicinity of the water/polypyrrole interface and its orientational relaxation time increased by one order of magnitude compared with bulk water, even when only one-third of the total polymer chains were oxidised. The results attained in this work were validated with experimental results, when they were available. Polypyrrole ring orientation and water orientation at the polypyrrole/water interface. (a) 256 rPPy and (b)171 rPPy,+,85 oPPy. [source] Molecular Dynamics Simulations of Polymer Translocations,MACROMOLECULAR THEORY AND SIMULATIONS, Issue 5 2004Richard Randel Abstract Summary: Molecular dynamics simulation studies of the translocation of charged homopolymers of length, N, driven by an electric potential gradient through a channel have been performed. We find that the translocation time, ,, displays an inverse power dependence on the temperature of the simulation ,,,,(T,,,T0),7/4, which is in very good agreement with experimental results. In addition, the dependence of , on the driving field strength and the velocity of translocation on the polymer length N have also been obtained. The results suggest that such minimalist models are useful in modelling biological processes and that the molecular dynamics method is a suitable approach for carrying out these simulations. Snapshot of the polymer during the simulation. [source] Molecular Dynamics Simulations of Polymer-Bonded Explosives (PBXs): Modeling, Mechanical Properties and their Dependence on Temperatures and Concentrations of BindersPROPELLANTS, EXPLOSIVES, PYROTECHNICS, Issue 5 2007Jijun Xiao Abstract Two models, i.e. "covering" and "cutting" models, for the polymer-bonded explosives (PBXs) were proposed for different researching aspects. Used for choosing polymeric binders, the "covering" models are mainly applied to find the relations of temperatures and concentrations respectively with elastic properties of the PBXs. The "cutting" model is especially used to describe the highly anisotropic behavior of 1,3,5-triamino-2,4,6-trinitrobenzene crystals (TATB). These models were realized by using molecular dynamics methods. It is found that the ductility of crystalline TATB can be effectively improved by blending fluorine-containing polymers in small amounts. The moduli for the PBXs decrease with increase in temperature and concentration of binders. Different crystalline surfaces interacting with the same polymer binder have different modulus-decreasing effects due to the highly anisotropic behavior of TATB. The modulus-decreasing effect for different crystalline surfaces ranking order is (010),(100)>(001). [source] Predicted Unfolding Order of the 13 ,-Helices in the Catalytic Domain of Glucoamylase from Aspergillusawamori var. X100 by Molecular Dynamics SimulationsBIOTECHNOLOGY PROGRESS, Issue 5 2003Hsuan-Liang Liu The unfolding mechanism of the 13 ,-helices in the catalytic domain of Aspergillus awamori var. X100 glucoamylase was investigated by 200 ps molecular dynamics simulations in explicit water with temperature jump technique. Rather than a simultaneous event, the unfolding of these 13 ,-helices followed a random ordered mechanism as ,8,,1,,11,,7,,10,,3,,12,,13,,4,,5,,9,,6,,2. No significant relationships were found between the unfolding order and the length and the hydrophobicity of the helix. ,-Helix 8 located in the inner region of the catalytic domain was predicted to be the first helix to unfold, indicating that the destruction of the secondary structure motif was initiated from the inner region of the catalytic domain. The dynamic behavior of these ,-helices induced by increased kinetic energy during the unfolding process is considered to be similar to the expansion and compression of a series of springs under the influence of mechanical stress. [source] Molecular Mechanism of the Hydration of Candida antarctica Lipase B in the Gas Phase: Water Adsorption Isotherms and Molecular Dynamics SimulationsCHEMBIOCHEM, Issue 18 2009Ricardo J. F. Branco Dr. Abstract Hydration is a major determinant of activity and selectivity of enzymes in organic solvents or in gas phase. The molecular mechanism of the hydration of Candida antarctica lipase B (CALB) and its dependence on the thermodynamic activity of water (aw) was studied by molecular dynamics simulations and compared to experimentally determined water sorption isotherms. Hydration occurred in two phases. At low water activity, single water molecules bound to specific water binding sites at the protein surface. As the water activity increased, water networks gradually developed. The number of protein-bound water molecules increased linearly with aw, until at aw=0.5 a spanning water network was formed consisting of 311 water molecules, which covered the hydrophilic surface of CALB, with the exception of the hydrophobic substrate-binding site. At higher water activity, the thickness of the hydration shell increased up to 10 Å close to aw=1. Above a limit of 1600 protein-bound water molecules the hydration shell becomes unstable and the formation of pure water droplets occurs in these oversaturated simulation conditions. While the structure and the overall flexibility of CALB was independent of the hydration state, the flexibility of individual loops was sensitive to hydration: some loops, such as those part of the substrate-binding site, became more flexible, while other parts of the protein became more rigid upon hydration. However, the molecular mechanism of how flexibility is related to activity and selectivity is still elusive. [source] The Binding Mode of Progesterone to Its Receptor Deduced from Molecular Dynamics SimulationsCHEMBIOCHEM, Issue 2-3 2003Tiziana Mordasini Dr. Abstract An unambiguous understanding of the binding mode of human progesterone to its receptor still eludes experimental search. According to the X-ray structure of the ligand-binding domain, only one (O3) of the two keto groups at the ligand ends (O3 and O20) should play a role. This result is in conflict with chemical intuition and the results of site-directed mutagenesis experiments. Herein, we report classical molecular dynamics simulations that reveal the dynamic nature of the binding in solution, elucidate the reasons why X-ray studies failed to determine the role of O20, and clarify the effects of the mutations. The predictive power of the force field is ensured by the consistent introduction of a first-principles representation of the ligand. [source] Probing the ,-Helical Structural Stability of Stapled p53 Peptides: Molecular Dynamics Simulations and AnalysisCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2010Zuojun Guo Reactivation of the p53 cell apoptosis pathway through inhibition of the p53-hDM2 interaction is a viable approach to suppress tumor growth in many human cancers and stabilization of the helical structure of synthetic p53 analogs via a hydrocarbon cross-link (staple) has been found to lead to increased potency and inhibition of protein,protein binding (J. Am. Chem. Soc. 129: 5298). However, details of the structure and dynamic stability of the stapled peptides are not well understood. Here, we use extensive all-atom molecular dynamics simulations to study a series of stapled ,-helical peptides over a range of temperatures in solution. The peptides are found to exhibit substantial variations in predicted ,-helical propensities that are in good agreement with the experimental observations. In addition, we find significant variation in local structural flexibility of the peptides with the position of the linker, which appears to be more closely related to the observed differences in activity than the absolute ,-helical stability. These simulations provide new insights into the design of ,-helical stapled peptides and the development of potent inhibitors of ,-helical protein,protein interfaces. [source] Activity Prediction and Structural Insights of Extracellular Signal-Regulated Kinase 2 Inhibitors with Molecular Dynamics SimulationsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2009Alberto Del Rio A computational application to predict, probe and interpret the activities of a series of congeneric compounds inhibiting extracellular signal-regulated kinase 2 protein kinase is presented. The study shows that molecular dynamics coupled with molecular mechanics Poisson,Boltzmann solvent accessible surface area free energy estimation is a suitable tool for investigating the experimental binding activities of ligands to protein kinases. Computed and experimental binding activities were found to be significantly correlated. Moreover, the interpretation of the X-ray co-crystal structure in conjunction with computational results shows that the hinge region of the protein insure the principal binding site via multiple hydrogen bonding interactions, whereas fine-modulation of biological activities along the series is accomplished through the combination of weak and strong interactions that compete with water. These are located in the substituent moieties of the ligands interfacing with the DFG motif, the sugar region and the hydrophobic pocket of extracellular signal-regulated kinase 2. The study suggests that a wider interaction framework that is well beyond the hinge region is required to predict and rationalize at molecular level the experimental biological activities of congeneric compound series. [source] Study of the Nature and Mechanism of the Rhombohedral-to-Cubic Phase Transition in ,-AlF3 with Molecular Dynamics Simulations.CHEMINFORM, Issue 21 2004Santanu Chaudhuri No abstract is available for this article. [source] Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics SimulationsCHEMISTRY - A EUROPEAN JOURNAL, Issue 45 2009Stéphane Téletchéa Dr. Abstract The antitumor drug cisplatin (cis -[PtCl2(NH3)2]) reacts with cellular DNA to form GG intrastrand adducts between adjacent guanines as predominant lesions. GGG sites have been shown to be hotspots of platination. To study the structural perturbation induced by binding of cisplatin to two adjacent guanines of a GGG trinucleotide, we examined here the decanucleotide duplex d[(G1C2C3G6T7 - C8G9C10),d(G11C12G13A14C15C16C17G18 - G19C20)] (dsCG*G*G) intrastrand cross-linked at the G* guanines by cis -{Pt(NH3)2}2+ using NMR spectroscopy and molecular dynamics (MD) simulations. The NMR spectra of dsCG*G*G were found to be similar to those of previously characterized DNA duplexes cross-linked by cisplatin at a pyG*G*X site (py=pyrimidine; X=C, T, A). This similarity of NMR spectra indicates that the base at the 3,-side of the G*G*,Pt cross-link does not affect the structure to a large extent. An unprecedented reversible isomerization between the duplex dsCG*G*G (bearing a ,Pt chelate) and duplex dsGG*G*T (bearing a ,Pt chelate) was observed, which yielded a 40:60 equilibrium between the two intrastrand GG,Pt cross-links. No formation of interstrand cross-links was observed. NMR spectroscopic data of dsCG*G*G indicated that the deoxyribose of the 5,-G* adopts an N-type conformation, and the cytidines C3, C15, and C16 have average phase angles intermediate between S and N. The NMR spectroscopic chemical shifts of dsGG*G*T showed some fundamental differences to those of pyG*G*,platinum adducts but were in agreement with the NMR spectra reported previously for the DNA duplexes cross-linked at an AG*G*C sequence by cisplatin or oxaliplatin. The presence of a purine instead of a pyrimidine at the 5,-side of the G*G* cross-link seems therefore to affect the structure of the XG* step significantly. [source] Molecular Dynamics Simulations of Na+/Cl, -Dependent Neurotransmitter Transporters in a Membrane-Aqueous SystemCHEMMEDCHEM, Issue 6 2007Anne Marie Jørgensen Abstract We have performed molecular dynamics simulations of a homology model of the human serotonin transporter (hSERT) in a membrane environment and in complex with either the natural substrate 5-HT or the selective serotonin reuptake inhibitor escitalopram. We have also included a transporter homologue, the Aquifex aeolicus leucine transporter (LeuT), in our study to evaluate the applicability of a simple and computationally attractive membrane system. Fluctuations in LeuT extracted from simulations are in good agreement with crystallographic B factors. Furthermore, key interactions identified in the X-ray structure of LeuT are maintained throughout the simulations indicating that our simple membrane system is suitable for studying the transmembrane protein hSERT in complex with 5-HT or escitalopram. For these transporter complexes, only relatively small fluctuations are observed in the ligand-binding cleft. Specific interactions responsible for ligand recognition, are identified in the hSERT,5HT and hSERT,escitalopram complexes. Our findings are in good agreement with predictions from mutagenesis studies. [source] Transport Processes at ,-Quartz,Water Interfaces: Insights from First-Principles Molecular Dynamics SimulationsCHEMPHYSCHEM, Issue 7 2008Waheed A. Adeagbo Dr. Abstract Car,Parrinello molecular dynamics (CP,MD) simulations are performed at high temperature and pressure to investigate chemical interactions and transport processes at the ,-quartz,water interface. The model system initially consists of a periodically repeated quartz slab with O-terminated and Si-terminated (1000) surfaces sandwiching a film of liquid water. At a temperature of 1000 K and a pressure of 0.3 GPa, dissociation of H2O molecules into H+ and OH, is observed at the Si-terminated surface. The OH, fragments immediately bind chemically to the Si-terminated surface while Grotthus-type proton diffusion through the water film leads to protonation of the O-terminated surface. Eventually, both surfaces are fully hydroxylated and no further chemical reactions are observed. Due to the confinement between the two hydroxylated quartz surfaces, water diffusion is reduced by about one third in comparison to bulk water. Diffusion properties of dissolved SiO2 present as Si(OH)4 in the water film are also studied. We do not observe strong interactions between the hydroxylated quartz surfaces and the Si(OH)4 molecule as would have been indicated by a substantial lowering of the Si(OH)4 diffusion coefficient along the surface. No spontaneous dissolution of quartz is observed. To study the mechanism of dissolution, constrained CP,MD simulations are done. The associated free energy profile is calculated by thermodynamic integration along the reaction coordinate. Dissolution is a stepwise process in which two SiO bonds are successively broken. Each bond breaking between a silicon atom at the surface and an oxygen atom belonging to the quartz lattice is accompanied by the formation of a new SiO bond between the silicon atom and a water molecule. The latter loses a proton in the process which eventually leads to protonation of the oxygen atom in the cleaved quartz SiO bond. The final solute species is Si(OH)4. [source] The Jahn,Teller Effect of the TiIII Ion in Aqueous Solution: Extended Ab Initio QM/MM Molecular Dynamics Simulations,CHEMPHYSCHEM, Issue 10 2004Chinapong Kritayakornupong Dr. Abstract Combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations, including only the first and the first and second hydration shells in the QM region, were performed for TiIIIin aqueous solution. The hydration structure of TiIIIis discussed in terms of radial distribution functions, coordination-number distributions and several angle distributions. Dynamical properties, such as librational and vibrational motions and TiIIIO vibrations, were evaluated. A fast dynamical Jahn,Teller effect of TiIII(aq) was observed in the QM/MM simulations, in particular when the second hydration shell was included into the QM region. The results justify the computational effort required for the inclusion of the second hydration shell into the QM region and show the importance of this effort for obtaining accurate hydration-shell geometries, dynamical properties, and details of the Jahn,Teller effect. [source] Molecular dynamics simulation of crack tip blunting in opposing directions along a symmetrical tilt grain boundary of copper bicrystalFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 11 2007A. LUQUE ABSTRACT Mode I crack growth along some grain boundaries of copper embrittled by solute segregation shows strong anisotropy. For instance, growth along the direction on the symmetrical tilt boundary has been reported to occur by intergranular brittle fracture, whereas growth along the opposite sense occurs in a ductile manner. In this paper, we simulate such crack configurations using molecular dynamics (embedded atom method [EAM]) in 3-dimensional perfect bicrystalline samples of pure copper of the aforementioned orientation at room temperature. In both cases the response is ductile, crack opening taking place by dislocation emission from the crack tip. The critical stress intensity factors (SIFs) for dislocation emission have been calculated by matching the displacement fields of the atoms in the tip neighbourhood with the continuum elastic fields. They are of the same order of magnitude for both growth senses despite the different morphology of their respective blunted crack tips and of the patterns of dislocations constituting their plastic zones. Thus, it seems that, in agreement with published results of continuum crystalline plasticity for the same problem, the plastic anisotropy associated with the different orientation of the slip systems with respect to the crack cannot in this case explain the experimental behaviour observed with solute embrittled bicrystals. [source] Molecular dynamics simulation of self-diffusion coefficient and its relation with temperature using simple Lennard-Jones potentialHEAT TRANSFER - ASIAN RESEARCH (FORMERLY HEAT TRANSFER-JAPANESE RESEARCH), Issue 2 2008Li Wei-Zhong Abstract The diffusion coefficient is indispensable to chemical engineering design and research. In practical engineering and research, there is still a great lack of available data. Therefore, methods need to be developed to solve this problem. In this paper, a molecular dynamics simulation method is used to predict the self-diffusion coefficient for a simple fluid by using the Green, Kubo relation (VACF) and the Einstein relation (MSD). The simulation results are in good agreement with experimental findings except for an error of about 10%. The algorithm average of the two methods (AV) reduces the error to 7%. The relationship of the diffusion coefficient with temperature has also been simulated. According to the simulation data, whose correlation is all above 0.99, the diffusion coefficient agrees well with temperature following the Arrenhius relationship. Activation energy for self-diffusion has been calculated and the result were 1258(VACF), 1272(MSD), and 1265(AV) J/mol separately. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res, 37(2): 86,93, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20191 [source] Molecular dynamics simulation on HP1 protein binding by histone H3 tail methylation and phosphorylationINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2009Yan-Ke Jiang Abstract Trimethylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging, and heterochromatin formation. Phosphorylation of histone H3 has been linked with mitotic chromatin condensation. During mitosis in vivo, H3 lysine 9 methylation and serine 10 phosphorylation can occur concomitantly on the same histone tail, whereas the influence of phosphorylation to trimethylation H3 tail recruiting HP1 remains controversial. In this work, molecular dynamics simulation of HP1 complexed with both trimethylated and phosphorylated H3 tail were performed and compared with the results from the previous methylated H3-HP1 trajectory. It is clear from the 10-ns dynamics simulation that two adjacent posttranslational modifications directly increase the flexibility of the H3 tail and weaken HP1 binding to chromatin. A combinatorial readout of two adjacent posttranslational modifications,a stable methylation and a dynamic phosphorylation mark,establish a regulatory mechanism of protein,protein interactions. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] Molecular dynamics simulation in the grand canonical ensembleJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 10 2007Hossein Eslami Abstract An extended system Hamiltonian is proposed to perform molecular dynamics (MD) simulation in the grand canonical ensemble. The Hamiltonian is similar to the one proposed by Lynch and Pettitt (Lynch and Pettitt, J Chem Phys 1997, 107, 8594), which consists of the kinetic and potential energies for real and fractional particles as well as the kinetic and potential energy terms for material and heat reservoirs interacting with the system. We perform a nonlinear scaling of the potential energy parameters of the fractional particle, as well as its mass to vary the number of particles dynamically. On the basis of the equations of motion derived from this Hamiltonian, an algorithm has been proposed for MD simulation at constant chemical potential. The algorithm has been tested for the ideal gas, for the Lennard,Jones fluid over a wide range of temperatures and densities, and for water. The results for the low-density Lennard,Jones fluid are compared with the predictions from a truncated virial equation of state. In the case of the dense Lennard,Jones fluid and water our predicted results are compared with the results reported using other available methods for the calculation of the chemical potential. The method is also applied to the case of vapor-liquid coexistence point predictions. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic siteJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2005Hirofumi Fujimoto Abstract Clustered DNA damage sites induced by ionizing radiation have been suggested to have serious consequences to organisms, such as cancer, due to their reduced probability to be repaired by the enzymatic repair machinery of the cell. Although experimental results have revealed that clustered DNA damage sites effectively retard the efficient function of repair enzymes, it remains unclear as to what particular factors influence this retardation. In this study, approaches based on molecular dynamics (MD) simulation have been applied to examine conformational changes and energetic properties of DNA molecules containing clustered damage sites consisting of two lesioned sites, namely 7,8-dihydro-8-oxoguanine (8-oxoG) and apurinic/apyrimidinic (AP) site, located within a few base pairs of each other. After 1 ns of MD simulation, one of the six DNA molecules containing a clustered damage site develops specific characteristic features: sharp bending at the lesioned site and weakening or complete loss of electrostatic interaction energy between 8-oxoG and bases located on the complementary strand. From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 788,798, 2005 [source] | |||||||||||||||||||||||||||||||||||||||||||